Moyer Jeffrey S, Maine Gabriel, Mulé James J
Department of Otolaryngology-Head and Neck Surgery, University of Michigan Medical Center, Ann Arbor, MI 48109-1904, USA.
Biol Blood Marrow Transplant. 2006 Oct;12(10):1010-9. doi: 10.1016/j.bbmt.2006.06.009.
Allogeneic bone marrow transplantation (BMT) remains the primary treatment for many hematologic malignancies but has had limited success against solid tumors. The antitumor activity of this treatment approach involves the tumoricidal activity of chemoradiation and the additive graft-versus-tumor activity of donor T cells. However, even with current protocols, some tumors develop resistance and become unresponsive to current therapeutic regimens. To address the problem of resistance and lack of solid tumor activity in allogeneic BMT, we undertook experiments to determine whether the graft-versus-tumor activity of donor T cells could be enhanced in the period immediately after allogeneic BMT with tumor lysate-pulsed dendritic cell (DC) vaccines. Using the B16 melanoma model, we found that the treatment of 6-day tumors with allogeneic BMT and 3 weekly vaccinations of tumor lysate-pulsed DCs starting 3 days after BMT had a significant effect on the growth of murine flank melanomas. This effect was tumor specific and occurred in the absence of full immune reconstitution as measured by donor T cell engraftment and cytotoxic T lymphocyte activity. In addition, DC vaccinations did not appear to exacerbate graft-versus-host disease. These experiments support the feasibility of DC vaccine strategies in the setting of allogeneic BMT.
异基因骨髓移植（BMT）仍然是许多血液系统恶性肿瘤的主要治疗方法，但对实体瘤的治疗效果有限。这种治疗方法的抗肿瘤活性涉及放化疗的杀肿瘤活性以及供体T细胞的附加移植物抗肿瘤活性。然而，即使采用目前的方案，一些肿瘤仍会产生耐药性并对当前的治疗方案无反应。为了解决异基因BMT中耐药性和实体瘤活性不足的问题，我们进行了实验，以确定在异基因BMT后立即使用肿瘤裂解物脉冲树突状细胞（DC）疫苗能否增强供体T细胞的移植物抗肿瘤活性。使用B16黑色素瘤模型，我们发现用异基因BMT治疗6天的肿瘤，并在BMT后3天开始每周接种3次肿瘤裂解物脉冲DC，对小鼠胁腹黑色素瘤的生长有显著影响。这种效应具有肿瘤特异性，并且在通过供体T细胞植入和细胞毒性T淋巴细胞活性测量的完全免疫重建缺失的情况下发生。此外，DC疫苗接种似乎不会加重移植物抗宿主病。这些实验支持了DC疫苗策略在异基因BMT中的可行性。
